Hofheinz Ralf-Dieter, Wenz Frederik, Lukan Nadine, Mai Sabine, Kripp Melanie, Staiger Wilko, Schwarzbach Matthias, Willeke Frank, Möhler Markus, Post Stefan, Hochhaus Andreas
Onkologisches Zentrum, III. Medizinische Klinik Mannheim, Medizinische Fakultät Mannheim der Universität Heidelberg, Heidelberg, Germany.
Int J Radiat Oncol Biol Phys. 2009 Jan 1;73(1):142-7. doi: 10.1016/j.ijrobp.2008.04.033. Epub 2008 Jun 6.
Adjuvant 5-fluorouracil-based chemoradiotherapy has been shown to improve the prognosis of gastric cancer. To optimize these results, in the present study oxaliplatin and capecitabine were used instead of 5-fluorouracil. We sought to determine the maximum tolerated dose and the dose-limiting toxicities (DLT) of these drugs in combination with intensity-modulated radiotherapy.
Patients with resected adenocarcinoma of the stomach or the gastroesophageal junction were included. They received two cycles of induction chemotherapy (oxaliplatin and capecitabine [XelOx] regimen). Using standard Phase I methodology, patients received 45 Gy in 1.8-Gy fractions either in combination with capecitabine 825 mg m(-1) twice a day (Dose Level [DL] I) or capecitabine in combination with weekly oxaliplatin 40 or 50 mg m(-1) (DL II and III). After the completion of chemoradiation, two additional cycles of XelOx were scheduled.
A total of 32 patients were recruited. Only 1 of 6 patients evaluable on DL I had DLT. Of the first 6 patients on DL II, 1 patient experienced DLT, and 3 of the remaining patients had Grade 3 toxicity. Therefore, DL II was defined as the maximum tolerated dose and a total of 20 patients were treated at this DL. The most frequently observed toxicities (Common Toxicity Criteria Grades 1, 2 and 3) were, respectively, leukocytopenia in 5, 5, and 4 patients; nausea in 3, 7, and 3; and diarrhea in 4, 0, and 1.
In summary, capecitabine 825 mg m(-1) twice a day (Days 1-33) and weekly oxaliplatin 40 mg m(-1) was safe and tolerable in combination with intensity-modulated radiotherapy. Furthermore, four cycles of XelOx could be applied before and after chemoradiotherapy in two thirds of the patients.
基于5-氟尿嘧啶的辅助放化疗已被证明可改善胃癌预后。为优化这些结果，在本研究中使用奥沙利铂和卡培他滨替代5-氟尿嘧啶。我们试图确定这些药物与调强放疗联合使用时的最大耐受剂量和剂量限制性毒性（DLT）。
纳入胃或胃食管交界腺癌切除术后患者。他们接受两个周期的诱导化疗（奥沙利铂和卡培他滨[XELOX]方案）。采用标准的I期方法，患者接受45 Gy，每次1.8 Gy，联合卡培他滨825 mg m(-1)，每日两次（剂量水平[DL]I），或卡培他滨联合每周一次奥沙利铂40或50 mg m(-1)（DL II和III）。放化疗完成后，计划再进行两个周期的XELOX。
共招募32例患者。DL I上可评估的6例患者中仅1例出现DLT。DL II上的前6例患者中，1例出现DLT，其余患者中有3例出现3级毒性。因此，DL II被定义为最大耐受剂量，共有20例患者在此剂量水平接受治疗。最常观察到的毒性（常见毒性标准1、2和3级）分别为：5例、5例和4例患者出现白细胞减少；3例、7例和3例患者出现恶心；4例、0例和1例患者出现腹泻。
总之，卡培他滨825 mg m(-1)，每日两次（第1 - 33天）和每周一次奥沙利铂40 mg m(-1)与调强放疗联合使用是安全且可耐受的。此外，三分之二的患者在放化疗前后可应用四个周期的XELOX。
